Immunophenotypic characteristics of diffuse large b-cell lymphoma and expression of C-MYC protein: single Ecuadorian center experience
DOI:
https://doi.org/10.35509/01239015.58Keywords:
Lymphoma, Large-Cell, Diffuse, Germinal Center, Proto-Oncogene Proteins c-myc, EcuadorAbstract
Background: Diffuse large B-cell lymphoma (DLBCL) makes up from 25% to 40% of all non- Hodgkin lymphomas (NHL) and is the most common histological subtype worldwide. In Ecuador, DLBCL makes up 49% of all NHL cases, but there have been no studies on the immunophenotypic classification of DLBCL in germinal center (GC) and non–germinal center (NGC) subtypes. This study was conducted to ascertain the immunophenotypic profile of DLBCL in an Ecuadorian hospital.
Methods: A total of 38 DLBCL cases from 2006 to 2015 were compiled from the Pathology Service at Metropolitan Hospital (HM) in Quito, Ecuador. Eleven of these cases failed to meet the inclusion criteria; thus, the final sample consisted of 27 cases. Manual tissue microarrays were constructed, and three immunohistochemical markers (CD10, BCL6, and MUM1) were applied according to the Hans algorithm; in addition, the expression of the c-myc protein expression was also investigated.
Results: The results showed that 77.8% of cases were of the GC subtype, 11.1% were NGC, and 11.1% were unclassifiable according to the Hans algorithm.
Conclusions: The most frequent DLBCL subtype was GC, with 21 cases; and 40.7% of these cases overexpressed c-myc.
Author Biographies
Johanna Cevallos, Hospital Metropolitano (Quito, Ecuador)
Laboratorio de Patología, Hospital Metropolitano, Quito, Ecuador
Nelson Montalvo, Hospital Metropolitano (Quito, Ecuador)
Laboratorio de Patología, Hospital Metropolitano, Quito, Ecuador
References
1. American Cancer Society. Linfoma no Hodgkin. Cancer Facts & Figures. Atlanta: American Society 2017; 21.
2. Ioachim H, Medeiros J. Nomenclature and classification of lymphomas. In: Ioachim ́s Lymph Node Pathology. 4th edition. Philadelphia: Wolters Kluwer; 2009. p. 296-305.
3. Cueva P, Yépez J. Sociedad de Lucha Contra el Cáncer/ Registro Nacional de Tumores. Epidemiología del cáncer en Quito 2006-2010. Quito; 2014. p. 152-62.
4. Stein H, Warnke RA, Chan WC, Jaffe ES, Chan JKC, Gatter KC et al. Diffuse large B-cell lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IACR Press; 2008. p. 233-7.
5. O'Malley D, Grimm K, Banks P. Inmunohistology of Non- Hodgkin Lymphoma. In: Dabbs D. Diagnostic Inmunohistochemistry. Theranostic and Genomic applications. 4th edition. Elsevier Saunders; 2014. p.148- 16.
6. Young K, Medeiros LJ, Chan W. Diffuse Large B-cell Lymphoma. In: Orazi A, Weiss L, Foucar K, Knowles D. Knowles' Neoplastic Hematopathology. 3th edition. Philadelphia: Wolters Kluwer; 2014. p. 502-56
7. Grande C. Actualización en el tratamiento del linfoma difuso de células grandes B. En: Fernández- Rañada J, Alegre A (Eds). Cuadernos de Hematología. 2011;1-15.
8. Hans CP, Weisenberger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by inmunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
https://doi.org/10.1182/blood-2003-05-1545
9. ChenY, XiaoL,ZhuX,LuC,YuB,FanD,etal. Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China. Zhonghua Bing Li Xue Za Zhi. 2014;43(6):383-8.
10. Chang ST, Chen SW, Ho CH, Kuo CC, Sakata S, Takeuchi K, et al. Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan. J Formos Med Assoc. 2016;115(11):961-7.
https://doi.org/10.1016/j.jfma.2016.09.006
11. Ospina JA. Caracterización de los pacientes con diagnóstico de Linfoma B Difuso de células grande en el Instituto de Cancerología [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2015.
12. Castellanos OW. Acuerdo intraobservador en estudios de inmunohistoquímica para Linfoma B difuso de célula grande según protocolo de Hans [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2012.
13. Silva FC. Valor pronóstico do perfil inmunotípico em linfoma difuso de grandes células B [tese de Mestrado]. Porto (Portugal): Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto; 2010. p. 1-18. J. Cevallos et al.
14. Perry AM, Molina-Kirsch H, Nathwani BN, Diebold J, Maclennan KA, Müller-Hermelink HK, et al. Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma. 2011;52(9):1681-8. 94.
https://doi.org/10.3109/10428194.2011.584254
15. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494-502.
https://doi.org/10.1158/1078-0432.CCR-09-0113
16. Gupta M, Maurer MJ, Wellik LE, Law ME, Han JJ, Ozsan N, et al. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP. Blood. 2012;120(22):4400-6.
https://doi.org/10.1182/blood-2012-05-428466
17. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. ClinOncol. 2012;30(28):3452-9.
https://doi.org/10.1200/JCO.2011.41.0985
18. Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, et al. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS One. 2012;7(4):e33813.
https://doi.org/10.1371/journal.pone.0033813
19. Batlle-López A, González de Villambrosía S, Francisco M, Malatxeberria S, Sáez A, Montalban C, et al. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker. Oncotarget. 2016;7(14):18036-49.
https://doi.org/10.18632/oncotarget.7495
20. Duncavage E, Advani RH, Agosti S, Foulis P, Gibson C, Kang L, et al. Template for Reporting Results of Biomarker Testing of Specimens from patients with diffuse large B-cell lymphoma, not otherwise specified. Arch Pathol Lab Med. 2016;140(11):1225-17.
https://doi.org/10.5858/arpa.2015-0418-CP
21. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan WC, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139(2):242-54.
https://doi.org/10.1309/AJCP2Z0TAGMUYJEB
22. Akyurek N, Uner A, Benekli M, Barista I. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 2012;118(17):4173-83.
https://doi.org/10.1002/cncr.27396
23. Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121(12):2253-63.
https://doi.org/10.1182/blood-2012-06-435842
24. Xu X, Zhang L, Wang Y, Zhang Q, Zhang L, Sun B, et al. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review. Int J Clin Exp Pathol. 2013;6(4):788-94
25. Mahmoud AZ, George TI, Czuchlewski DR, Zhang QY, Wilson CS, Sever CE, et al. Scoring of MYC protein Expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists. Mod Pathol. 2015;28(4):545-51.
https://doi.org/10.1038/modpathol.2014.140
2. Ioachim H, Medeiros J. Nomenclature and classification of lymphomas. In: Ioachim ́s Lymph Node Pathology. 4th edition. Philadelphia: Wolters Kluwer; 2009. p. 296-305.
3. Cueva P, Yépez J. Sociedad de Lucha Contra el Cáncer/ Registro Nacional de Tumores. Epidemiología del cáncer en Quito 2006-2010. Quito; 2014. p. 152-62.
4. Stein H, Warnke RA, Chan WC, Jaffe ES, Chan JKC, Gatter KC et al. Diffuse large B-cell lymphoma, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IACR Press; 2008. p. 233-7.
5. O'Malley D, Grimm K, Banks P. Inmunohistology of Non- Hodgkin Lymphoma. In: Dabbs D. Diagnostic Inmunohistochemistry. Theranostic and Genomic applications. 4th edition. Elsevier Saunders; 2014. p.148- 16.
6. Young K, Medeiros LJ, Chan W. Diffuse Large B-cell Lymphoma. In: Orazi A, Weiss L, Foucar K, Knowles D. Knowles' Neoplastic Hematopathology. 3th edition. Philadelphia: Wolters Kluwer; 2014. p. 502-56
7. Grande C. Actualización en el tratamiento del linfoma difuso de células grandes B. En: Fernández- Rañada J, Alegre A (Eds). Cuadernos de Hematología. 2011;1-15.
8. Hans CP, Weisenberger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by inmunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
https://doi.org/10.1182/blood-2003-05-1545
9. ChenY, XiaoL,ZhuX,LuC,YuB,FanD,etal. Immunohistochemical classification and prognosis of diffuse large B-cell lymphoma in China. Zhonghua Bing Li Xue Za Zhi. 2014;43(6):383-8.
10. Chang ST, Chen SW, Ho CH, Kuo CC, Sakata S, Takeuchi K, et al. Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan. J Formos Med Assoc. 2016;115(11):961-7.
https://doi.org/10.1016/j.jfma.2016.09.006
11. Ospina JA. Caracterización de los pacientes con diagnóstico de Linfoma B Difuso de células grande en el Instituto de Cancerología [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2015.
12. Castellanos OW. Acuerdo intraobservador en estudios de inmunohistoquímica para Linfoma B difuso de célula grande según protocolo de Hans [tesis de investigación]. Bogotá: Universidad Nacional de Colombia; 2012.
13. Silva FC. Valor pronóstico do perfil inmunotípico em linfoma difuso de grandes células B [tese de Mestrado]. Porto (Portugal): Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto; 2010. p. 1-18. J. Cevallos et al.
14. Perry AM, Molina-Kirsch H, Nathwani BN, Diebold J, Maclennan KA, Müller-Hermelink HK, et al. Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system. Leuk Lymphoma. 2011;52(9):1681-8. 94.
https://doi.org/10.3109/10428194.2011.584254
15. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17):5494-502.
https://doi.org/10.1158/1078-0432.CCR-09-0113
16. Gupta M, Maurer MJ, Wellik LE, Law ME, Han JJ, Ozsan N, et al. Expression of Myc, but not pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with epratuzumab/R-CHOP. Blood. 2012;120(22):4400-6.
https://doi.org/10.1182/blood-2012-05-428466
17. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. ClinOncol. 2012;30(28):3452-9.
https://doi.org/10.1200/JCO.2011.41.0985
18. Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, et al. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS One. 2012;7(4):e33813.
https://doi.org/10.1371/journal.pone.0033813
19. Batlle-López A, González de Villambrosía S, Francisco M, Malatxeberria S, Sáez A, Montalban C, et al. Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker. Oncotarget. 2016;7(14):18036-49.
https://doi.org/10.18632/oncotarget.7495
20. Duncavage E, Advani RH, Agosti S, Foulis P, Gibson C, Kang L, et al. Template for Reporting Results of Biomarker Testing of Specimens from patients with diffuse large B-cell lymphoma, not otherwise specified. Arch Pathol Lab Med. 2016;140(11):1225-17.
https://doi.org/10.5858/arpa.2015-0418-CP
21. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan WC, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139(2):242-54.
https://doi.org/10.1309/AJCP2Z0TAGMUYJEB
22. Akyurek N, Uner A, Benekli M, Barista I. Prognostic significance of MYC, BCL2, and BCL6 rearrangements in patients with diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab. Cancer. 2012;118(17):4173-83.
https://doi.org/10.1002/cncr.27396
23. Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121(12):2253-63.
https://doi.org/10.1182/blood-2012-06-435842
24. Xu X, Zhang L, Wang Y, Zhang Q, Zhang L, Sun B, et al. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review. Int J Clin Exp Pathol. 2013;6(4):788-94
25. Mahmoud AZ, George TI, Czuchlewski DR, Zhang QY, Wilson CS, Sever CE, et al. Scoring of MYC protein Expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists. Mod Pathol. 2015;28(4):545-51.
https://doi.org/10.1038/modpathol.2014.140
How to Cite
[1]
Cevallos, J. and Montalvo, N. 2019. Immunophenotypic characteristics of diffuse large b-cell lymphoma and expression of C-MYC protein: single Ecuadorian center experience. Revista Colombiana de Cancerología. 23, 2 (Jun. 2019), 41–44. DOI:https://doi.org/10.35509/01239015.58.
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2019-06-25
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